Field of the Invention
The invention relates to a pipette device having a micro-dosing unit, a pipette unit, which has at least one pipette tip which can be mounted exchangeably on the pipette unit and an expulsion end, a positioning means, and a control means.
Description of Related Art
A pipette device of the type in question may have, in principle, merely a single pipette tip at a coupling point. However, such a pipette device is usually a multi-channel pipette device, in which the pipette unit thus has a plurality of coupling points and a corresponding number of pipette tips that can be mounted at said coupling points. Such a multi-channel pipette device is often used on an automated pipetter or pipette robot.
By appropriate activation of a displacement unit in the pipette unit, which displacement unit is usually formed in the manner of a cylinder-piston arrangement, liquid can be suctioned into or expelled from the pipette tips through the discharge openings thereof.
In the case of a typical pipette device of the type in question the pipette unit is brought into different operating positions by way of a positioning means. The positioning means may be an X/Y/Z movement means. It may also be the arm of a robot, which can be moved back and forth in space, largely freely. The prior art gives various suggestions for this.
In the case of a pipette device of the type in question the pipette tips are picked up in a take-up position from a tip store, i.e., are coupled to the coupling points. The pipette unit is then moved by way of the positioning means into a liquid take-up position. In order to take up the liquid into the pipette tips, i.e., in order to aspirate said liquid, the discharge openings of the pipette tips are dipped into the liquid in corresponding vessels, for example the cells of a microtitre plate. The liquid is taken up by the effect of the displacement unit or units in the pipette unit.
If the liquid take-up is complete, the pipette unit is moved by way of the positioning means into a liquid delivery position. There, the desired liquid volume is delivered from the respective pipette tip into a target vessel, again by way of the effect of the displacement unit or units. Here, too, the vessels may again be wells of a microtitre plate.
The liquid may be delivered in greater volumes as a free-flowing jet. In the case of small volumes perhaps even contact must be made between the target vessel and the pipette tip so that the adhesion force of the liquid drop at the pipette tip can be overcome. The aforementioned boundary conditions downwardly limit the liquid volumes that can be delivered to volumes in the region of a few microliters. Metered delivery quantities in the nanoliter range thus cannot be provided. In addition, in the case of the conventional automated pipetter, there is the risk of carrying over substances already located in the target vessel.
Once the liquid has been delivered in the delivery position, a remaining volume in the pipette tips is removed from time to time. For this purpose the pipette unit is brought by way of the positioning means into an expelling position, in which the rest of the liquid in the pipette tips is then expelled, again by way of the displacement unit.
Following the delivery of the remaining liquid, the pipette unit is brought into a pipette tip discarding position. There, the pipette tips are released from the coupling points on the pipette unit by way of a tip discarding means and are discarded into a collection container.
In the prior art forming the starting point of the invention (International Patent Application Publication WO 2006/076957 A1 and corresponding U.S. Pat. No. 8,071,049), comprehensive prior art has been described concerning the question of lower minimal volumes to be delivered in the case of a pipette device of the type in question. In addition, a pipette device that enables the delivery of volumes down to the nanoliter range is described in this prior art.
In the prior art discussed here, a pipette tip is connected to a resiliently deformable tube as expulsion end on the pipette tip. This tube, at the lower end, forms the discharge opening of the pipette tip. This resiliently deformable tube may be deformed by a movable actuation means of a micro-dosing unit such that a defined liquid volume can be selectively expelled by the deformation of the tube just above the discharge opening of the pipette tip. Due to the resultant volume change inside the tube, liquid is expelled from the discharge opening of the pipette tip as free-flowing drops or as a free-flowing jet. Thus, it is possible to expel extremely small volumes in the nanoliter range. For this purpose, reference may also be made to the information in the aforementioned prior art.
In the prior art, a micro-dosing unit of the pipette device is an arrangement having clamping jaws as abutment for the movable actuation means, which itself is driven piezoelectrically. For further details, reference is also made in this regard to International Patent Application Publication WO 2005/016534 A1 for a micro-dosing unit of this type, said document disclosing details regarding the structure of such a micro-dosing unit.
In the prior art forming the starting point of the invention, the micro-dosing unit of the pipette device is located in a stationary manner in the liquid delivery position. The pipette tip must be threaded from above into the actuation means of the micro-dosing unit. The liquid within the pipette tip is drawn into the tube by capillary forces. An expulsion of liquid in small sub-volumes from a pipette tip into a plurality of different target vessels requires a movement of the target vessels relative to the pipette tips arranged in a stationary manner in the liquid delivery position.
The previously described pipette device is consequently suitable in theory for delivering extremely small volumes at different locations, but as a pipette device in practical use it can still be optimized.